Recent studies from our laboratory have revealed that MSH increases tyrosinase synthesis by, at most, 2-fold, while the specific activity of the enzyme may increase to levels which are 100 times control values. This discrepancy between synthesis rates and tyrosinase activity may be the result of an MSH-induced activation process. We have found that cytosol preparations from MSH-treated melanoma cell cultures can increase tyrosinase activity in untreated melanoma homogenates. Further, results from competitive ELISA analysis of several melanoma cell lines, which differ in the basal level of tyrosinase activity, have revealed the amelanotic cell cultures have higher levels of catalytically less active tyrosinase that melanotic cells. We have also obtained evidence that melanoma cell homogenates contain a factor which can reduce the activity of purified tyrosinase. Taken together, these results suggest that MSH may increase tyrosinase activity in melanoma cell cultures by both increasing the rate of enzyme synthesis and by promoting the appearance of a regulatory factor which increases the catalytic activity of pre-existing tyrosinase. (M)